title: Signal transducer and activator of transcription 3 (STAT3) and Suppressor of Cytokine Signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in decidual-like natural killer cell line NK-92.
abstract: OBJECTIVES  In previous studies, we have shown that sHLA-G reduces cytotoxicity of decidual NK cells, which was dependent upon reduction in signal transducer and activator of transcription 3 (STAT3) and perforin. In this study, we aimed to confirm the role of STAT3 for induction of cytotoxicity and to analyze the regulative role of its antagonist suppressor of cytokine signaling 3 (SOCS3). Furthermore, the influence of both factors on cytokine expression should be analyzed. METHODS  All experiments were performed on NK-92 cells. STAT3 and SOCS3 have been silenced using two different small interfering RNA sequences each. Silencing efficiency and STAT3 tyrosine phosphorylation have been analyzed by Western blotting. Cytotoxicity to K562 target cells has been assessed by flow cytometry. Expression of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α, and TNF-β has been measured using cytometric bead arrays for flow cytometry. RESULTS  STAT3 and SOCS3 have been successfully silenced. STAT3 silencing reduced cytotoxicity. SOCS3 silencing induced increase in STAT3 tyrosine phosphorylation and cytotoxicity. STAT3 silencing reduced IL-10 expression significantly, while SOCS3 silencing induced, also significantly, the opposite effect. The other cytokines were expressed at very low concentration or not constantly affected. CONCLUSION  STAT3 and SOCS3 are involved in regulation of NK cell cytotoxicity and IL-10 expression.
authors.affiliation: Placenta-Labor, Department of Obstetrics, Friedrich-Schiller-University, Jena, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Braunschweig
authors.forename: Tobias G
authors.initials: TG
authors.lastname: Poehlmann
authors.forename: Susann
authors.initials: S
authors.lastname: Busch
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Schleussner
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003656:Decidua / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing / Q000187:drug effects / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016753:Interleukin-10; D014443:Tyrosine